Publications by authors named "Anna Kaminska"

187 Publications

SYNGAP1-DEE: A visual sensitive epilepsy.

Clin Neurophysiol 2021 Feb 3;132(4):841-850. Epub 2021 Feb 3.

Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, Paris Descartes University, Paris, France; Department of Paediatric Neurology, Necker-Enfants Malades Hospital, University of Paris, AP-HP, Paris, France. Electronic address:

Objective: To further delineate the electroclinical features of individuals with SYNGAP1 pathogenic variants.

Methods: Participants with pathogenic SYNGAP1 variants and available video-electroencephalogram (EEG) recordings were recruited within five European epilepsy reference centers. We obtained molecular and clinical data, analyzed EEG recordings and archived video-EEGs of seizures and detailed characteristics of interictal and ictal EEG patterns for every patient.

Results: We recruited 15 previously unreported patients and analyzed 72 EEGs. Two distinct EEG patterns emerged, both triggered by eye closure. Pattern 1 (14/15 individuals) consisted of rhythmic posterior/diffuse delta waves appearing with eye-closure and persisting until eye opening (strongly suggestive of fixation-off sensitivity). Pattern 2 (9/15 individuals) consisted of diffuse polyspike-and-wave discharges triggered by eye closure (eye-closure sensitivity). Both patterns presented in 8/15. Including archived video-EEG clips of seizures from 9/15 patients, we analyzed 254 seizures. Of 224 seizures experienced while awake, 161 (72%) occurred at or following eye closure. In 119/161, pattern 1 preceded an atypical absence, myoclonic seizure or myoclonic absence; in 42/161, pattern 2 was associated with eyelid myoclonia, absences and myoclonic or atonic seizures.

Conclusions: Fixation-off and eye closure were the main triggers for seizures in this SYNGAP1 cohort.

Significance: Combining these clinical and electroencephalographic features could help guide genetic diagnosis.
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http://dx.doi.org/10.1016/j.clinph.2021.01.014DOI Listing
February 2021

Jerking during absences: video-EEG and polygraphy of epileptic myoclonus associated with two paediatric epilepsy syndromes.

Epileptic Disord 2021 Feb 25. Epub 2021 Feb 25.

Department of Clinical Neurophysiology, Necker-Enfants Malades Hospital, APHP, Paris, France.

Epileptic myoclonus (EM) is reported in many paediatric epilepsies from neonatal period to adolescence. Myoclonus can be the only seizure type or may occur among others, independently or in combination as a single ictal event. We report two children presenting with absences associated with myoclonus, predominating on one side, in a setting of two different types of absence seizures and two different electro-clinical syndromes. Patients were explored with long-duration video-EEG coupled to surface EMG polygraphy. EEG was visually analysed and complemented by jerk-locked back-averaging. Two types of seizure, encompassing myoclonus and absence, were identified: myoclonic absences in the context of epilepsy with myoclonic absences and atypical absences with atonic component (negative myoclonus) in the context of encephalopathy related to status epilepticus during slow sleep (ESES). In the latter case, rhythmic upper limb jerking, mimicking positive myoclonus, corresponded to recovery of muscular tone after each negative myoclonus. Due to the rhythmic recovery of muscle tone, subsequent rhythmic negative myoclonus may exhibit a similar clinical picture to that of rhythmic positive myoclonus. Video-EEG recording coupled to EMG polygraphy is essential in order to precisely characterize motor manifestations during seizures with myoclonus [Published with video sequences].
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http://dx.doi.org/10.1684/epd.2021.1240DOI Listing
February 2021

Deep phenotyping unstructured data mining in an extensive pediatric database to unravel a common KCNA2 variant in neurodevelopmental syndromes.

Genet Med 2021 Jan 26. Epub 2021 Jan 26.

Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades hospital, Universite de Paris, Paris, France.

Purpose: Electronic health records are gaining popularity to detect and propose interdisciplinary treatments for patients with similar medical histories, diagnoses, and outcomes. These files are compiled by different nonexperts and expert clinicians. Data mining in these unstructured data is a transposable and sustainable methodology to search for patients presenting a high similitude of clinical features.

Methods: Exome and targeted next-generation sequencing bioinformatics analyses were performed at the Imagine Institute. Similarity Index (SI), an algorithm based on a vector space model (VSM) that exploits concepts extracted from clinical narrative reports was used to identify patients with highly similar clinical features.

Results: Here we describe a case of "automated diagnosis" indicated by Dr. Warehouse, a biomedical data warehouse oriented toward clinical narrative reports, developed at Necker Children's Hospital using around 500,000 patients' records. Through the use of this warehouse, we were able to match and identify two patients sharing very specific clinical neonatal and childhood features harboring the same de novo variant in KCNA2.

Conclusion: This innovative application of database clustering clinical features could advance identification of patients with rare and common genetic conditions and detect with high accuracy the natural history of patients harboring similar genetic pathogenic variants.
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http://dx.doi.org/10.1038/s41436-020-01039-zDOI Listing
January 2021

The phenotypic spectrum of X-linked, infantile onset ALG13-related developmental and epileptic encephalopathy.

Epilepsia 2021 Feb 7;62(2):325-334. Epub 2021 Jan 7.

Institute of Human Genetics, University of Leipzig Medical Center, Leipzig, Germany.

Objective: Asparagine-linked glycosylation 13 (ALG13) deficiencies have been repeatedly described in the literature with the clinical phenotype of a developmental and epileptic encephalopathy (DEE). Most cases were females carrying the recurrent ALG13 de novo variant, p.(Asn107Ser), with normal transferrin electrophoresis.

Methods: We delineate the phenotypic spectrum of 38 individuals, 37 girls and one boy, 16 of them novel and 22 published, with the most common pathogenic ALG13 variant p.(Asn107Ser) and additionally report the phenotype of three individuals carrying other likely pathogenic ALG13 variants.

Results: The phenotypic spectrum often comprised pharmacoresistant epilepsy with epileptic spasms, mostly with onset within the first 6 months of life and with spasm persistence in one-half of the cases. Tonic seizures were the most prevalent additional seizure type. Electroencephalography showed hypsarrhythmia and at a later stage of the disease in one-third of all cases paroxysms of fast activity with electrodecrement. ALG13-related DEE was usually associated with severe to profound developmental delay; ambulation was acquired by one-third of the cases, whereas purposeful hand use was sparse or completely absent. Hand stereotypies and dyskinetic movements including dystonia or choreoathetosis were relatively frequent. Verbal communication skills were absent or poor, and eye contact and pursuit were often impaired.

Significance: X-linked ALG13-related DEE usually manifests as West syndrome with severe to profound developmental delay. It is predominantly caused by the recurrent de novo missense variant p.(Asn107Ser). Comprehensive functional studies will be able to prove or disprove an association with congenital disorder of glycosylation.
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http://dx.doi.org/10.1111/epi.16761DOI Listing
February 2021

Progressive External Ophthalmoplegia in Polish Patients-From Clinical Evaluation to Genetic Confirmation.

Genes (Basel) 2020 Dec 31;12(1). Epub 2020 Dec 31.

Department of Neurology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland.

Mitochondrial encephalomyopathies comprise a group of heterogeneous disorders resulting from impaired oxidative phosphorylation (OxPhos). Among a variety of symptoms progressive external ophthalmoplegia (PEO) seems to be the most common. The aim of this study is to present clinical and genetic characteristics of Polish patients with PEO. Clinical, electrophysiological, neuroradiological, and morphological data of 84 patients were analyzed. Genetic studies of mitochondrial DNA (mtDNA) were performed in all patients. Among nuclear DNA (nDNA) genes was sequenced in 41 patients, () in 13 patients, and in 2 patients. Total of 27 patients were included in the chronic progressive external ophthalmoplegia (CPEO) group, 24 in the CPEO+ group. Twenty-six patients had mitochondrial encephalomyopathy (ME), six patients Kearns-Sayre syndrome (KSS), and one patient sensory ataxic neuropathy, dysarthria, ophthalmoparesis (SANDO) syndrome. Genetic analysis of nDNA genes revealed the presence of pathogenic or possibly pathogenic variants in the gene in nine patients, the gene in five patients and the gene in two patients. Detailed patients' history and careful assessment of family history are essential in the diagnostic work-up. Genetic studies of both mtDNA and nDNA are necessary for the final diagnosis of progressive external ophthalmoplegia and for genetic counseling.
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http://dx.doi.org/10.3390/genes12010054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7824435PMC
December 2020

De novo mutations of are responsible for arthrogryposis broadening the -related phenotypes.

J Med Genet 2020 Sep 14. Epub 2020 Sep 14.

Institut National de la Santé et de la Recherche Médicale (Inserm), UMR-1195, Université Paris Saclay, Le Kremlin Bicêtre, 94276, France

Background: Arthrogryposis multiplex congenita (AMC) is the direct consequence of reduced fetal movements. AMC includes a large spectrum of diseases which result from variants in genes encoding components required for the formation or the function of the neuromuscular system. AMC may also result from central nervous involvement. encodes Nav1.1, a critical component of voltage-dependent sodium channels which underlie action potential generation and propagation. Variants of are known to be responsible for Dravet syndrome, a severe early-onset epileptic encephalopathy. We report pathogenic heterozygous missense de novo variants in in three unrelated individuals with AMC.

Methods: Whole-exome sequencing was performed from DNA of the index case of AMC families. Heterozygous missense variants in (p.Leu893Phe, p.Ala989Thr, p.Ile236Thr) were identified in three patients. Sanger sequencing confirmed the variants and showed that they occurred de novo.

Results: AMC was diagnosed from the second trimester of pregnancy in the three patients. One of them developed drug-resistant epileptic seizures from birth. We showed that is expressed in both brain and spinal cord but not in skeletal muscle during human development. The lack of motor denervation as established by electromyographic studies or pathological examination of the spinal cord or skeletal muscle in the affected individuals suggests that AMC is caused by brain involvement.

Conclusion: We show for the first time that variants are responsible for early-onset motor defect leading to AMC indicating a critical role of in prenatal motor development and broadening the phenotypic spectrum of variants in .
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http://dx.doi.org/10.1136/jmedgenet-2020-107166DOI Listing
September 2020

Reliability and accuracy of EEG interpretation for estimating age in preterm infants.

Ann Clin Transl Neurol 2020 09 7;7(9):1564-1573. Epub 2020 Aug 7.

BABA Center, Department of Clinical Neurophysiology, Children's Hospital, Helsinki University Hospital, University of Helsinki, Helsinki, Finland.

Objectives: To determine the accuracy of, and agreement among, EEG and aEEG readers' estimation of maturity and a novel computational measure of functional brain age (FBA) in preterm infants.

Methods: Seven experts estimated the postmenstrual ages (PMA) in a cohort of recordings from preterm infants using cloud-based review software. The FBA was calculated using a machine learning-based algorithm. Error analysis was used to determine the accuracy of PMA assessments and intraclass correlation (ICC) was used to assess agreement between experts.

Results: EEG recordings from a PMA range 25 to 38 weeks were successfully interpreted. In 179 recordings from 62 infants interpreted by all human readers, there was moderate agreement between experts (aEEG ICC = 0.724; 95%CI:0.658-0.781 and EEG ICC = 0.517; 95%CI:0.311-0.664). In 149 recordings from 61 infants interpreted by all human readers and the FBA algorithm, random and systematic errors in visual interpretation of PMA were significantly higher than the computational FBA estimate. Tracking of maturation in individual infants showed stable FBA trajectories, but the trajectories of the experts' PMA estimate were more likely to be obscured by random errors. The accuracy of visual interpretation of PMA estimation was compromised by neurodevelopmental outcome for both aEEG and EEG review.

Interpretation: Visual assessment of infant maturity is possible from the EEG or aEEG, with an average of human experts providing the highest accuracy. Tracking PMA of individual infants was hampered by errors in experts' estimates. FBA provided the most accurate maturity assessment and has potential as a biomarker of early outcome.
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http://dx.doi.org/10.1002/acn3.51132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7480927PMC
September 2020

Aortic stiffness-Is kynurenic acid a novel marker? Cross-sectional study in patients with persistent atrial fibrillation.

PLoS One 2020 31;15(7):e0236413. Epub 2020 Jul 31.

Chair and Department of Experimental and Clinical Pharmacology, Laboratory of Cellular and Molecular Pharmacology, Medical University of Lublin, Lublin, Poland.

Objective: Although a number of modifiable and non-modifiable causes were implicated in arterial stiffness, its pathogenesis remains elusive, and very little is known about aortic elasticity in supraventricular arrhythmias. The potential role of disturbed kynurenine metabolism in the pathogenesis of cardiovascular disease has been recently suggested. Thus, we studied the correlations of aortic stiffness and echocardiographic parameters with biochemical markers and serum level of kynurenic acid (KYNA), an endothelial derivative of tryptophan, formed along the kynurenine pathway, among patients with atrial fibrillation (AF).

Methods: Study cohort comprised 100 patients with persistent AF (43 females/57 males). Arterial stiffness index (ASI), structural and functional indices of left atrium (LA) and left ventricle (LV) were evaluated electrocardiographically. Biochemical analyses included the measurements of serum KYNA (HPLC) and of the selected markers of lipids and glucose metabolism, thyroid status, kidney function, inflammation and coagulation.

Results: KYNA (β = 0.389, P = 0.029), homocysteine (β = 0.256, P = 0.40), total cholesterol (β = 0.814; P = 0.044), LDL (β = 0.663; P = 0.44), TSH (β = 0.262, P = 0.02), fT3 (β = -0.333, P = 0.009), fT4 (β = -0.275, P = 0.043) and creatinine (β = 0.374, P = 0.043) were independently correlated with ASI. ASI was also independently associated with LV end-systolic diameter (LVEDd; β = 1.751, P = 0.045), midwall fractional shortening (mFS; β = -1.266, P = 0.007), ratio mFS/end-systolic stress (mFS/ESS; β = -0.235, P = 0.026), LV shortening fraction (FS; β = -0.254, P = 0.017), and LA volume index (LAVI; β = 0.944, P = 0.022).

Conclusions: In patients with AF, aortic stiffness correlated positively with KYNA, biochemical risk factors of atherosclerosis and with the indices of diastolic dysfunction of LV and LA. Revealed relationship between ASI and KYNA is an original observation, suggesting a potential role of disturbed kynurenine metabolism in the pathogenesis of arterial stiffening. KYNA, synthesis of which is influenced by homocysteine, emerges as a novel, non-classical factor associated with ASI in patients with AF.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0236413PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7394382PMC
September 2020

Neonatal factors related to survival and intellectual and developmental outcome of patients with early-onset urea cycle disorders.

Mol Genet Metab 2020 06 19;130(2):110-117. Epub 2020 Mar 19.

Reference Center of Inherited Metabolic Diseases, Necker Enfants Malades Hospital, APHP, Imagine Institute, Paris Descartes University, Paris, France.

Purpose: We aimed to identify prognostic factors for survival and long-term intellectual and developmental outcome in neonatal patients with early-onset urea cycle disorders (UCD) experiencing hyperammonaemic coma.

Methods: We retrospectively analysed ammonia (NH3) and glutamine levels, electroencephalogram and brain images obtained during neonatal coma of UCD patients born between 1995 and 2011 and managed at a single centre and correlated them to survival and intellectual and developmental outcome.

Results: We included 38 neonates suffering from deficiencies of argininosuccinate synthetase (ASSD, N = 12), ornithine transcarbamylase (OTCD, N = 10), carbamoylphosphate synthetase 1 (CPSD, N = 7), argininosuccinate lyase (ASLD, N = 7), N-acetylglutamate synthase (NAGS, N = 1) or arginase (ARGD, N = 1). Symptoms occurred earlier in mitochondrial than in cytosolic UCD. Sixty-eight percent of patients survived, with a mean (standard deviation-SD) follow-up of 10.4 (5.3) years. Mortality was mostly observed in OTCD (N = 7/10) and CPSD (N = 4/7) patients. Plasma NH3 level during the neonatal period, expressed as area under the curve, but not glutamine level was associated with mortality (p = .044 and p = .610). 62.1% of the patients had normal intellectual and developmental outcome. Intellectual and developmental outcome tended to correlate with UCD subtype (p = .052). No difference in plasma NH3 or glutamine level during the neonatal period among developmental outcomes was identified. EEG severity was linked to UCD subtypes (p = .004), ammonia levels (p = .037), duration of coma (p = .043), and mortality during the neonatal period (p = .020). Status epilepticus was recorded in 6 patients, 3 of whom died neonatally, 1 developed a severe intellectual disability while the 2 last patients had a normal development.

Conclusion: UCD subtypes differed by survival rate, intellectual and developmental outcome and EEG features in the neonatal period. Hyperammonaemia expressed as area under the curve was associated with survival but not with intellectual and developmental outcome whereas glutamine was not associated with one of these outcomes. Prognostic value of video-EEG monitoring and the association between status epilepticus and mortality should be assessed in neonatal hyperammonaemic coma in further studies.
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http://dx.doi.org/10.1016/j.ymgme.2020.03.003DOI Listing
June 2020

Social and emotional intelligence as a basis for communicative resource formation in family caregivers of patients with endogenous mental disorders.

Wiad Lek 2020 ;73(1):107-112

National Pirogov Memorial Medical University, Vinnytsia, Ukraine.

Objective: The aim of our study was to determine features of social and emotional intelligence in family caregivers of patients with endogenous mental disorders as a basis for communicative resource formation in family where a patient lives.

Patients And Methods: Materials and methods: A total of 273 family caregivers of patients with paranoid schizophrenia and bipolar disorder were involved into this survey under informed consent conditions. Control group included 55 mentally healthy respondents, in whose families there is no mentally sick family member. Emotional intelligence of family caregivers was measured using the psychodiagnostic test "EQ" by N. Hall. To assess level of social intelligence the J. Gilford and M. Sullivan test (in adaptation done by Mikhailova E.S.) was used. Values of p <0.05 were considered significant.

Results: Results: The study revealed that family caregivers of patients with schizophrenia and affective disorders demonstrate a decrease in emotional and social intelligence indicators, which creates significant obstacles for effective interpersonal family communication and for the harmonious functioning of a family, in which a mentally sick patient lives, in general. Difficulties of emotional regulation, emotional management, recognition of emotional states of other participants of communication related to the level of emotional and social intelligence of FC are factors, that complicate interpersonal relations in families of patients and reduce possibilities for psychosocial adaptation of all family members.

Conclusion: Conclusions: Revealed features should be taken into consideration when creating appropriate psycho-educational and psycho-corrective programs for family caregivers of patients with endogenous mental disorders.
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March 2020

Focal seizures with a migrating aspect in infants treated with beta-lactam antibiotics - Report of two cases.

Neurophysiol Clin 2020 Apr 7;50(2):81-86. Epub 2020 Feb 7.

Department of Clinical Neurophysiology, Necker-Enfants-Malades Hospital, AP-HP, 149, rue de Sèvres, 75743 Paris cedex 15, France. Electronic address:

Seizures caused by beta-lactam antibiotics are relatively rare. However, they represent a clinically significant phenomenon and have been widely reported in all age groups. Here we describe two infants presenting subtle multifocal seizures with a migrating aspect on EEG during beta-lactam antibiotic treatment with agents from the carbapenem group (meropenem) and the cephalosporin group (ceftazidime).
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http://dx.doi.org/10.1016/j.neucli.2020.01.003DOI Listing
April 2020

Children and adolescents with epilepsy in rehabilitation centers: A French prospective transversal study.

Epilepsy Behav 2020 03 24;104(Pt A):106898. Epub 2020 Jan 24.

Epilepsy Observatory, Paris, France; Department of Clinical Neurophysiology, Hopital Necker-Enfants Malades, APHP, Paris, France; Medical Social Educative Rehab Centre "les Côteaux", 61400 Mortagne au Perche, France; INSERM U 1141, Neurodiderot, Paris, France.

Introduction: The reason why some children and adolescent with epilepsy (CAWE) still challenge the "inclusive" educative policy needs to be explored.

Methods/patients: We conducted a transversal study in French medical, social, and educative rehab centers (MSERCs) dedicated to CAWE to describe the profile of 263 centers-involved (CI)-CAWE. Centers-involved CAWE were prospectively followed from September 2012 to August 2013. Medical, social, and educative rehab centers were dichotomized according to their care-provider agreement (i.e., CAWE of "moderate" (M) vs. "severe" (S) conditions). Clinical factors known to impact clinical outcome and quality of life (QoL) in epilepsy and four disabling conditions at risk to impact school life (i.e., cognitive and psychiatric/behavioral disorders, risk of physical hazards (i.e., refractory seizures with unpredictable loss of tone and/or awareness), and one or more seizure/week) were evaluated. The electronic chart of the French collaborative database (namely GRENAT) was used for data collection allowing comparison with the profile of 731 "normally integrated and schooled" (NIS)-CAWE extracted from GRENAT and matching for generation (i.e., born between 1988 and 2006).

Results: Centers-involved CAWE's profile was found, after adjustment, to be associated with clinical factors and disabling conditions reflecting the poorest clinical outcome and health-related quality of life (HR-QoL) (all p < 0.001). A cutoff of two disabilities/child highly discriminated NIS-CAWE vs. CI-CAWE. Centers-involved CAWE of S-MSERCs were the most severe (all p < 0.001), and the type of cognitive disability (i.e., intellectual disability (ID) vs. specific learning disorders (SLD)) highly paralleled the types of MSERCs (S vs. M). Using a parent-informant questionnaire, the number of disabilities/child was found to correlate with both the evaluation of the impact of epilepsy (r = 0.47, p < 0.001) and the HR-QoL (r = 0.37, p < 0.001). A satisfactory social life was reported (83.8%) even after S vs. M dichotomization (77.2% vs. 94.7%; p < 0.001).

Conclusion: Multiple disabilities rather than epilepsy per se challenge the inclusive educative policy. Evaluation of disabilities could be the missing bridge to optimize this policy and understand its limits.
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http://dx.doi.org/10.1016/j.yebeh.2019.106898DOI Listing
March 2020

Epilepsy with migrating focal seizures: KCNT1 mutation hotspots and phenotype variability.

Neurol Genet 2019 Dec 25;5(6):e363. Epub 2019 Oct 25.

Service de Génétique (G.B., J.-P.B., S.G.-L.), Groupe Hospitalier Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM U1163 (G.B., N.B-.B., R.N.), Université Paris Descartes, PRES Sorbonne Paris Cité, Paris, France; Service de Neurologie Pédiatrique (N.C., N.B-.B., A.K., R.N.), Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Centre de Référence des Epilepsies Rares (N.C., A.K., R.N.), Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; INSERM U1129 (N.N., A.K., R.N.), Paris, France; Service de Neurophysiologie Clinique et Pédiatrie (M.K.), INSERM U1099, Hôpital Universitaire de Rennes, Université de Rennes, France; Service de Neurophysiologie Clinique (M.E., A.K.), Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Service de Génétique Clinique (V.C.), Hôpital Femme Mère Enfant, Metz-Thionville, France; Pediatric Neurology Research Group (A.M.), Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain; Service de Génétique Clinique (L.L.), Hôpital d'Enfants, CHU de Nancy, Vandoeuvre-Lès-Nancy, France; Service de Pédiatrie (F.D.), CHU de Grenoble, France; Service de Neurologie Pédiatrique (D.D., T.B.V.), Hôpital Trousseau, Assistance Publique-Hôpitaux de Paris, Paris, France; Service de Neurologie Pédiatrique (N.V., M.M.), APHM, Hôpital d'Enfants de La Timone, Marseille, France; Service de Neurologie Pédiatrique (M-.A.B., M.M.), Centre Hospitalier Universitaire de Tours, Tours, France; Département de Génétique (C.N., M.M.), Hôpital Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, Paris, France; Service de Radiologie Pédiatrique (N.B., M.M.), Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; Université Aix-Marseille (M.M.), INSERM, MMG, UMR-S 1251, Faculté de Médecine, Marseille, France; and Unité de Neurologie Pédiatrique (S.A.), Hôpital Rober Debré, Assistance Publique-Hôpitaux de Paris, Paris, France.

Objective: To report new sporadic cases and 1 family with epilepsy of infancy with migrating focal seizures (EIMFSs) due to KCNT1 gain-of-function and to assess therapies' efficacy including quinidine.

Methods: We reviewed the clinical, EEG, and molecular data of 17 new patients with EIMFS and mutations, in collaboration with the network of the French reference center for rare epilepsies.

Results: The mean seizure onset age was 1 month (range: 1 hour to 4 months), and all children had focal motor seizures with autonomic signs and migrating ictal pattern on EEG. Three children also had infantile spasms and hypsarrhythmia. The identified variants clustered as "hot spots" on the C-terminal domain, and all mutations occurred de novo except the p.R398Q mutation inherited from the father with nocturnal frontal lobe epilepsy, present in 2 paternal uncles, one being asymptomatic and the other with single tonic-clonic seizure. In 1 patient with EIMFS, we identified the p.R1106Q mutation associated with Brugada syndrome and saw no abnormality in cardiac rhythm. Quinidine was well tolerated when administered to 2 and 4-year-old patients but did not reduce seizure frequency.

Conclusions: The majority of the mutations appear to cluster in hot spots essential for the channel activity. A same mutation can be linked to a spectrum of conditions ranging from EMFSI to asymptomatic carrier, even in the same family. None of the antiepileptic therapies displayed clinical efficacy, including quinidine in 2 patients.
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http://dx.doi.org/10.1212/NXG.0000000000000363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6878841PMC
December 2019

Features of subjective perception of social support by patients with endogenous mental disorders.

Wiad Lek 2019 ;72(9 cz 2):1747-1751

National Pirogov Memorial Medical University, Vinnytsia, Ukraine.

Objective: Introduction: Previous research shows that the role of perceived social support, defined as individuals' confidence of the availability of adequate support when needed, is considered as a protective external resource to promote better adaptation in psychiatric patients. The aim of our study was to reveal the features of patients with endogenous mental disorders regarding their ability to perceive social support.

Patients And Methods: Materials and methods: A total of 168 patients with schizophrenia (F.20) and 75 patients with affective disorders (F30.F.33) were involved into this study under informed consent conditions. Control group included 55 mentally healthy respondents. Perceived social support was measured using Multidimensional Scale of Perceived Social Support (MSPSS) by Zimet (1998).

Results: Results: Family, friends and significant others become main donors of social support for patients with endogenous mental disorders. Meanwhile, perceived social support in patients with schizophrenia is mostly coming from family. In patients with affective disorders, indicators of perceived social support from friends and significant others are significantly higher compared to patients with schizophrenia (P <0.001). Revealed features can be used while developing appropriate psychoeducational programs for patients with endogenous mental disorders.

Conclusion: Conclusions: On the basis of revealed data, the key features of ability to perceive social support in patients with endogenous mental disorders, depending on the duration of the disease, were determined. It has been revealed that ability to perceive social support in patients with endogenous mental disorders decreases with prolongation of duration of the disease.
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November 2019

The needle EMG findings in myotonia congenita.

J Electromyogr Kinesiol 2019 Dec 3;49:102362. Epub 2019 Oct 3.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

Introduction: Myotonia congenita (MC) is caused by pathogenic variants in the CLCN1 gene coding the chloride channel protein.

Methods: To test the hypothesis that needle EMG could be helpful in distinguishing between the recessive and dominant MC, we performed EMG examination in 36 patients (23 men) aged 4-61 years with genetically proven MC: in 30 patients with autosomal recessive MC (Becker MC) and in 6 with autosomal dominant MC (Thomsen MC).

Results: Myotonic discharges were recorded in 95.8% of examined muscles. For the whole MC group we observed a significant positive correlation between parameters of motor unit activity potentials (MUAPs) in vastus lateralis and tibialis anterior muscles and the duration of the disease. Similar correlation for biceps brachii also was found in Becker MC subgroup only.

Discussion: EMG could still be helpful in diagnosis of MC and together with provocative tests might be useful in differentiation between recessive and autosomal MC.
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http://dx.doi.org/10.1016/j.jelekin.2019.102362DOI Listing
December 2019

KCNT1 epilepsy with migrating focal seizures shows a temporal sequence with poor outcome, high mortality and SUDEP.

Brain 2019 10;142(10):2996-3008

Reference Centre for Rare Epilepsies, Department of Pediatric Neurology, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France.

Epilepsy of infancy with migrating focal seizures was first described in 1995. Fifteen years later, KCNT1 gene mutations were identified as the major disease-causing gene of this disease. Currently, the data on epilepsy of infancy with migrating focal seizures associated with KCNT1 mutations are heterogeneous and many questions remain unanswered including the prognosis and the long-term outcome especially regarding epilepsy, neurological and developmental status and the presence of microcephaly. The aim of this study was to assess data from patients with epilepsy in infancy with migrating focal seizures with KCNT1 mutations to refine the phenotype spectrum and the outcome. We used mind maps based on medical reports of children followed in the network of the French reference centre for rare epilepsies and we developed family surveys to assess the long-term outcome. Seventeen patients were included [age: median (25th-75th percentile): 4 (2-15) years, sex ratio: 1.4, length of follow-up: 4 (2-15) years]. Seventy-one per cent started at 6 (1-52) days with sporadic motor seizures (n = 12), increasing up to a stormy phase with long lasting migrating seizures at 57 (30-89) days. The others entered this stormy phase directly at 1 (1-23) day. Ten patients entered a consecutive phase at 1.3 (1-2.8) years where seizures persisted at least daily (n = 8), but presented different semiology: brief and hypertonic with a nocturnal (n = 6) and clustered (n = 6) aspects. Suppression interictal patterns were identified on the EEG in 71% of patients (n = 12) sometimes from the first EEG (n = 6). Three patients received quinidine without reported efficacy. Long-term outcome was poor with neurological sequelae and active epilepsy except for one patient who had an early and long-lasting seizure-free period. Extracerebral symptoms probably linked with KCNT1 mutation were present, including arteriovenous fistula, dilated cardiomyopathy and precocious puberty. Eight patients (47%) had died at 3 (1.5-15.4) years including three from suspected sudden unexpected death in epilepsy. Refining the electro-clinical characteristics and the temporal sequence of epilepsy in infancy with migrating focal seizures should help diagnosis of this epilepsy. A better knowledge of the outcome allows one to advise families and to define the appropriate follow-up and therapies. Extracerebral involvement should be investigated, in particular the cardiac system, as it may be involved in the high prevalence of sudden unexpected death in epilepsy in these cases.
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http://dx.doi.org/10.1093/brain/awz240DOI Listing
October 2019

SCAMP5 mutation causes a neurodevelopmental disorder with autistic features and seizures.

J Med Genet 2020 02 22;57(2):138-144. Epub 2019 Aug 22.

INSERM UMR1163, Institut IMAGINE, Paris, France

Background: Autistic spectrum disorders (ASDs) with developmental delay and seizures are a genetically heterogeneous group of diseases caused by at least 700 different genes. Still, a number of cases remain genetically undiagnosed.

Objective: The objective of this study was to identify and characterise pathogenic variants in two individuals from unrelated families, both of whom presented a similar clinical phenotype that included an ASD, intellectual disability (ID) and seizures.

Methods: Whole-exome sequencing was used to identify pathogenic variants in the two individuals. Functional studies performed in the model was used to assess the protein function in vivo.

Results: Probands shared a heterozygous de novo secretory carrier membrane protein (SCAMP5) variant (NM_001178111.1:c.538G>T) resulting in a p.Gly180Trp missense variant. belongs to a family of tetraspanin membrane proteins found in secretory and endocytic compartments of neuronal synapses. In the fly SCAMP orthologue, the p.Gly302Trp genotype corresponds to human p.Gly180Trp. Western blot analysis of proteins overexpressed in the fat body showed strongly reduced levels of the SCAMP p.Gly302Trp protein compared with the wild-type protein, indicating that the mutant either reduced expression or increased turnover of the protein. The expression of the fly homologue of the human p.Gly180Trp mutation caused similar eye and neuronal phenotypes as the expression of SCAMP RNAi, suggesting a dominant-negative effect.

Conclusion: Our study identifies SCAMP5 deficiency as a cause for ASD and ID and underscores the importance of synaptic vesicular trafficking in neurodevelopmental disorders.
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http://dx.doi.org/10.1136/jmedgenet-2018-105927DOI Listing
February 2020

ANO5 mutations in the Polish limb girdle muscular dystrophy patients: Effects on the protein structure.

Sci Rep 2019 08 8;9(1):11533. Epub 2019 Aug 8.

Laboratory of Molecular Basis of Cell Motility, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 3 Pasteur St., 02-093, Warsaw, Poland.

LGMD2L is a subtype of limb-girdle muscular dystrophy (LGMD), caused by recessive mutations in ANO5, encoding anoctamin-5 (ANO5). We present the analysis of five patients with skeletal muscle weakness for whom heterozygous mutations within ANO5 were identified by whole exome sequencing (WES). Patients varied in the age of the disease onset (from 22 to 38 years) and severity of the morphological and clinical phenotypes. Out of the nine detected mutations one was novel (missense p.Lys132Met, accompanied by p.His841Asp) and one was not yet characterized in the literature (nonsense, p.Trp401Ter, accompanied by p.Asp81Gly). The p.Asp81Gly mutation was also identified in another patient carrying a p.Arg758Cys mutation as well. Also, a c.191dupA frameshift (p.Asn64LysfsTer15), the first described and common mutation was identified. Mutations were predicted by in silico tools to have damaging effects and are likely pathogenic according to criteria of the American College of Medical Genetics and Genomics (ACMG). Indeed, molecular modeling of mutations revealed substantial changes in ANO5 conformation that could affect the protein structure and function. In addition, variants in other genes associated with muscle pathology were identified, possibly affecting the disease progress. The presented data indicate that the identified ANO5 mutations contribute to the observed muscle pathology and broaden the genetic spectrum of LGMD myopathies.
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http://dx.doi.org/10.1038/s41598-019-47849-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687736PMC
August 2019

Effect of hyperglycemia on cerebral blood flow in patients with diabetes.

Diabetes Res Clin Pract 2019 Jul 28;153:1-5. Epub 2019 May 28.

Department of Pathophysiology of Hearing and Balance, Ludwig Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University, Toruń, Poland.

Aims: Diabetes interferes with cerebral blood flow (CBF) and it seems that the effect of acute hyperglycemia on CBF is different from the changes in CBF caused by chronic diabetes. The aim of the study was to check whether there are changes in CBF measured using transcranial Doppler (TCD) in patients with hyperglycemia before and after normalization of glycemia.

Methods: The study involved 29 patients with diabetes and 27 healthy subjects (control group). The TCD test evaluated mean flow velocity (Vm), systolic velocity (Vs) and Gosling's pulsatility index (PI) in both middle cerebral arteries (MCAs). It was performed twice in patients with diabetes (during hyperglycemia and after normalization of glycemia) and once in the control group.

Results: The baseline blood flow parameters were similar in both groups. After the normalization of glycemia in patients with diabetes, they showed lower values of Vm and Vs compared to the control group (p < 0.001). Also, the normalization of glycemia caused a decrease in Vm and Vs (p < 0.001) in patients with diabetes. There were no significant differences in PI.

Conclusions: In the patients with hyperglycemia, Vm and Vs in the MCA were higher than during normoglycemia, which was probably related to vasoconstriction and hypervolemia.
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http://dx.doi.org/10.1016/j.diabres.2019.05.024DOI Listing
July 2019

Screening for late-onset Pompe disease in Poland.

Acta Neurol Scand 2019 Oct 18;140(4):239-243. Epub 2019 Jun 18.

Department of Neurology, Medical University of Warsaw, Warsaw, Poland.

Objectives: We aimed to screen for late-onset Pompe disease using the dried blood spot (DBS) test in a cohort of patients with limb-girdle muscle weakness or persistent hyperCKemia.

Materials And Methods: Patients with limb-girdle muscle weakness, persistently elevated CK, rigid spine syndrome, dyspnoea, myalgia or sibling of the patient diagnosed with LOPD were included in the study. Acid α-glucosidase (GAA) activity was measured on DBS by tandem mass spectrometry and followed by genetic testing when required. Study was conducted between June 2014 and May 2017.

Results: A total of 337 patients aged 32.2 years (range 2-80) were included in the study. Late-onset Pompe disease was diagnosed in 10 patients (3.0% of tested cohort). All were compound heterozygotes with common c.32-13T>G mutation on one allele and missense or frameshift mutation on the other. Two of the mutations (c.1951delG and c.397T>G) were not reported previously. Seven of the patients started enzyme replacement therapy.

Conclusions: DBS test is a reliable method for screening for late-onset Pompe disease.
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http://dx.doi.org/10.1111/ane.13133DOI Listing
October 2019

Dopaminergic Genes Polymorphisms and Prefrontal Cortex Efficiency Among Obese People - Whether Gender is a Differentiating Factor?

Curr Mol Med 2019 ;19(6):405-418

Chair and Department of Clinical Neuropsychology, Nicolaus Copernicus University in Torun, Collegium Medicum in Bydgoszcz, Poland.

Background: Obesity is a chronic condition associated with poorer cognitive functioning. Wisconsin Card Sorting Test (WCST) is a useful tool for evaluating executive functions. In this study, we assessed the association between dopaminergic gene polymorphisms: DAT1 (SLC6A3), COMTVal158Met, DRD4 (48-bp variable number of tandem repeats - VNTR) and WCST parameters to investigate the functions of the frontal lobes in obese individuals.

Objective: To find the significant correlations between polymorphisms of DAT1, COMTVal158Met, DRD4 and executive functions in obese subjects.

Methods: The analysis of the frequency of individual alleles was performed in 248 obese patients (179 women, 69 men). Evaluation of the prefrontal cortex function (operating memory and executive functions) was measured with the Wisconsin Card Sorting Test (WCST). Separate analyzes were performed in age subgroups to determine different activities and regulation of genes in younger and older participants.

Results: Scores of WCST parameters were different in the subgroups of women and men and in the age subgroups. Regarding the COMT gene, patients with A/A and G/A polymorphisms showed significantly better WCST results in WCST_P, WCST_CC and WCST_1st. Regarding DAT1 men with L/L and L/S made less non-perseverative errors, which was statistically significant. In DRD4, significantly better WCST_1st results were found only in older women with S allele.

Conclusion: Obtained results indicate the involvement of dopaminergic transmission in the regulation of prefrontal cortex function. Data analysis indicates that prefrontal cortex function may ensue, from different elements such as genetic factors, metabolic aspects of obesity, and hormonal activity (estrogen).
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http://dx.doi.org/10.2174/1566524019666190424143653DOI Listing
August 2020

The Association Between Affective Temperament Traits and Dopamine Genes in Obese Population.

Int J Mol Sci 2019 Apr 15;20(8). Epub 2019 Apr 15.

Chair and Department of Clinical Neuropsychology, Nicolaus Copernicus University in Toruń, Collegium Medicum, Bydgoszcz 85-094, Poland.

Studies indicate the heritable nature of affective temperament, which shows personality traits predisposing to the development of mental disorders. Dopaminergic gene polymorphisms such as , Val158Met, and have been linked to affective disorders in obesity. Due to possible correlation between the aforementioned polymorphisms and the affective temperament, the aim of our research was to investigate this connection in an obese population. The study enrolled 245 obese patients (178 females; 67 males). The affective temperament was assessed using the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego autoquestionnaire (TEMPS-A). Genetic polymorphisms of , Val158Met and were collected from peripheral blood sample and determined using a polymerase chain reaction (PCR). Only in COMT polymorphisms, the cyclothymic and irritable dimensions were significantly associated with Met/Val carriers ( = 0.04; = 0.01). Another interesting finding was the correlation between the affective temperament and age in men and women. We assume that dopamine transmission in heterozygotes of COMT may determine the role of the affective temperament in obese persons. Dopaminergic transmission modulated by COMT may be responsible for a greater temperament expression in obese individuals. To our knowledge, this is the first study describing the role of affective temperament in the obese population, but more research is needed in this regard.
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http://dx.doi.org/10.3390/ijms20081847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6515197PMC
April 2019

Motor Unit Number Index (MUNIX) as a biomarker of motor unit loss in post-polio syndrome versus needle EMG.

J Electromyogr Kinesiol 2019 Jun 9;46:35-40. Epub 2019 Mar 9.

Department of Neurology, Medical University of Warsaw, 02-097 Warsaw, Banacha 1A str., Poland.

MUNIX method (Motor Unit Number Index) had been not used to assess number of motor neurons in post-polio syndrome in contrary to needle electromyography.

Objectives: To confirm if MUNIX reflects motor unit loss and clinical stage and to assess difference in MUNIX and EMG results between muscles in different stage.

Methods: 132 Muscles (MUNIX) and 96 (EMG) in 12 patients were studied and divided into groups: with normal strength(N), stable weakness and atrophy(S), new weakness and atrophy(W).

Results: In PPS group MUNIX global was 561.36 ± 282.6 (right 6 muscles) and 561.27 ± 281.1 (left) significantly lower than in control group (six muscles 1139.6 ± 164.5) (p < 0.05). MUNIX global correlated with MRC global. MUNIX was greater in muscles with normal strength (95-100% of normal values) than in those with stable weakness (48%-0% of normal values) and new weakness (65%-0% of normal values). Respectively to clinical stage of muscle MUP (motor unit potential) amplitude increased to 350% of normal value, from 250% to 110%, and from 300% to 700%. No correlation was found between MUP parameters and MRC values.

Conclusions: MUNIX reflects motor dysfunction and could be a good biomarker for loss of motor neurons in PPS.
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http://dx.doi.org/10.1016/j.jelekin.2019.03.006DOI Listing
June 2019

Quantitative analysis and EEG markers of KCNT1 epilepsy of infancy with migrating focal seizures.

Epilepsia 2019 01 7;60(1):20-32. Epub 2018 Dec 7.

INSERM Unit U1129 Infantile Epilepsies and Brain Plasticity, University Paris Descartes, Sorbonne Paris Cité, Paris, France.

Objective: We aimed to characterize epilepsy of infancy with migrating focal seizures (EIMFS), a rare, severe early onset developmental epilepsy related to KCNT1 mutation, and to define specific electroencephalography (EEG) markers using EEG quantitative analysis. The ultimate goal would be to improve early diagnosis and to better understand seizure onset and propagation of EIMFS as compared to other early onset developmental epilepsy.

Methods: EEG of 7 EIMFS patients with KCNT1 mutations (115 seizures) and 17 patients with other early onset epilepsies (30 seizures) was included in this study. After detection of seizure onset and termination, spatiotemporal characteristics were quantified. Seizure propagation dynamics were analyzed using chronograms and phase coherence.

Results: In patients with EIMFS, seizures started and were localized predominantly in temporal and occipital areas, and evolved with a stable frequency (4-10 Hz). Inter- and intrahemispheric migrations were present in 60% of EIMFS seizures with high intraindividual reproducibility of temporospatial dynamics. Interhemispheric migrating seizures spread in 71% from temporal or occipital channels to the homologous contralateral ones, whereas intrahemispheric seizures involved mainly frontotemporal, temporal, and occipital channels. Causality links were present between ictal activities detected under different channels during migrating seizures. Finally, time delay index (based on delays between the different ictal onsets) and phase correlation index (based on coherence of ictal activities) allowed discrimination of EIMFS and non-EIMFS seizures with a specificity of 91.2% and a sensitivity of 84.4%.

Significance: We showed that the migrating pattern in EIMFS is not a random process, as suggested previously, and that it is a particular propagation pattern that follows the classical propagation pathways. It is notable that this study reveals specific EEG markers (time delay and phase correlation) accessible to visual evaluation, which will improve EIMFS diagnosis.
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http://dx.doi.org/10.1111/epi.14605DOI Listing
January 2019

Early and long-term electroclinical features of patients with epilepsy and PCDH19 mutation.

Epileptic Disord 2018 Dec;20(6):457-467

Pediatric Neurology Department, Centre de Référence des Épilepsies Rares, Necker Enfants Malades Hospital, Paris, Inserm U1129, Paris; University Paris Descartes; CEA, Gif sur Yvette.

Protocadherin 19 (PCDH19) mutations have been identified in epilepsy in females with mental retardation as well as patients with a "Dravet-like" phenotype. We aimed to elucidate the electroclinical phenotype associated with PCDH19 mutation, which is currently difficult to identify at onset leading to a delay in diagnosis. We retrospectively reviewed clinical and EEG data for 13 consecutive patients with PCDH19 mutations or deletions diagnosed at our centers from 2009 to 2011, and followed these patients into adolescence and adulthood. We identified a specific temporal sequence of electroclinical manifestations, identified as three main stages. During the first two years of life, previously healthy girls presented with clusters of afebrile focal seizures. Early seizures were recorded on video-EEG in 10/13 patients, and were focal (n=8) with temporo-occipital and frontal onset. Three patients with strictly stereotyped focal seizures underwent a pre-surgical work-up. Two patients started with generalized seizures, one presenting with early-onset atypical absences and the other generalized tonic-clonic seizures. During the course of the disease, from two to 10 years, seizures became fever-sensitive and continued to recur in clusters, although these were less frequent. Seizures were mainly described by eyewitnesses as generalized tonic-clonic, even though three of five seizures, recorded on EEG, showed a focal onset with fast bilateral spread. Atypical absences and fever-induced tonic-clonic seizures remained frequent in only one patient until the age of 16 years. No specific treatment or combination appeared to be more effective over another. Various degrees of cognitive or behavioural impairment were reported for all patients, but it was in the second decade that behavioural disturbances prevailed with hetero-aggressiveness and behaviour associated with frontal lobe abnormalities leading to psychosis in two. Early recognition of the above features should improve early diagnosis and long-term management of patients with epilepsy and PCDH19 mutations.
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http://dx.doi.org/10.1684/epd.2018.1009DOI Listing
December 2018

The frequency of mitochondrial polymerase gamma related disorders in a large Polish population cohort.

Mitochondrion 2019 07 10;47:179-187. Epub 2018 Nov 10.

Department of Medical Genetics, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland; Department of Pediatrics, Nutrition and Metabolic Disorders, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland.

Diseases related to DNA polymerase gamma dysfunction comprise of heterogeneous clinical presentations with variable severity and age of onset. Molecular screening for the common POLG variants: p.Ala467Thr, p.Trp748Ser, p.Gly848Ser, and p.Tre251Ile has been conducted in a large population cohort (n = 3123) and in a clinically heterogeneous group of 1289 patients. Recessive pathogenic variants, including six novel ones were revealed in 22/26 patients. Infantile Alpers-Huttenlocher syndrome and adulthood ataxia spectrum were the most common found in our group. Distinct molecular profile identified in the Polish patients with significant predominance of p.Trp748Ser variant (50% of mutant alleles) reflected strikingly low population frequency of the three remaining variants and slightly higher p.Trp748Ser allele frequency in the general Polish population as compared to the non-Finish European population.
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http://dx.doi.org/10.1016/j.mito.2018.11.004DOI Listing
July 2019

Correction: IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.

Genet Med 2019 Aug;21(8):1897-1898

INSERM, U 1127, CNRS UMR 7225, Sorbonne Universites, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle epiniere, ICM, Paris, France.

This Article was originally published under Nature Research's License to Publish, but has now been made available under a CC BY 4.0 license. The PDF and HTML versions of the Article have been modified accordingly.
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http://dx.doi.org/10.1038/s41436-018-0327-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608434PMC
August 2019

IQSEC2-related encephalopathy in males and females: a comparative study including 37 novel patients.

Genet Med 2019 04 12;21(4):837-849. Epub 2018 Sep 12.

INSERM, U 1127, CNRS UMR 7225, Sorbonne Universites, UPMC Univ Paris 06 UMR S 1127, Institut du Cerveau et de la Moelle epiniere, ICM, Paris, France.

Purpose: Variants in IQSEC2, escaping X inactivation, cause X-linked intellectual disability with frequent epilepsy in males and females. We aimed to investigate sex-specific differences.

Methods: We collected the data of 37 unpublished patients (18 males and 19 females) with IQSEC2 pathogenic variants and 5 individuals with variants of unknown significance and reviewed published variants. We compared variant types and phenotypes in males and females and performed an analysis of IQSEC2 isoforms.

Results: IQSEC2 pathogenic variants mainly led to premature truncation and were scattered throughout the longest brain-specific isoform, encoding the synaptic IQSEC2/BRAG1 protein. Variants occurred de novo in females but were either de novo (2/3) or inherited (1/3) in males, with missense variants being predominantly inherited. Developmental delay and intellectual disability were overall more severe in males than in females. Likewise, seizures were more frequently observed and intractable, and started earlier in males than in females. No correlation was observed between the age at seizure onset and severity of intellectual disability or resistance to antiepileptic treatments.

Conclusion: This study provides a comprehensive overview of IQSEC2-related encephalopathy in males and females, and suggests that an accurate dosage of IQSEC2 at the synapse is crucial during normal brain development.
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http://dx.doi.org/10.1038/s41436-018-0268-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6752297PMC
April 2019

Introducing system of psychotherapeutic interventions for family caregivers of patients with endogenous mental disorders.

Wiad Lek 2018;71(5):980-985

National Pirogov Memorial Medical University, Vinnytsya, Ukraine.

Objective: Introduction: Providing care for patients with endogenous mental disorders is associated with significant psychosocial burden. The aim of this study was to introduce a system of psychotherapeutic interventions for family caregivers of patients with paranoid schizophrenia and bipolar disorder based on understanding their prevalent coping behavior patterns and communicative coping resources evaluation.

Patients And Methods: Materials and methods: A total of 273 family caregivers of patients with paranoid schizophrenia and bipolar disorder were involved into this survey under informed consent conditions. Control group included 55 mentally healthy respondents, in whose families there is no mentally sick family member. Test for psychological diagnostics of coping mechanisms (E. Heim) and emotional empathy test (А. Mehrabian) were chosen as psychological testing research tools. Values of p <0.05 were considered significant.

Results: Results: The study revealed prevalence of certain maladaptive coping strategies and lack of communicative coping resources in family caregivers of patients with paranoid schizophrenia and bipolar disorder. These data might be among significant predictors of communicative dysfunctions in families where one of the family members has endogenous mental disorder, and must be considered while developing appropriate psychotherapeutic programs.

Conclusion: Conclusions: On the basis of revealed data, we have introduced an integrative system of psychotherapeutic interventions, aimed to develop adaptive forms of coping behavior in family caregivers, increase their empathetic and affiliative resources, create favorable conditions for activation of personal resources and adaptive potential of both family caregivers and patients with paranoid schizophrenia and bipolar disorder.
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March 2019

Intraspinal Transplantation of the Adipose Tissue-Derived Regenerative Cells in Amyotrophic Lateral Sclerosis in Accordance with the Current Experts' Recommendations: Choosing Optimal Monitoring Tools.

Stem Cells Int 2018 12;2018:4392017. Epub 2018 Aug 12.

Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawinskiego Str, 02-106 Warsaw, Poland.

Stem cells (SCs) may constitute a perspective alternative to pharmacological treatment in neurodegenerative diseases. Although the safety of SC transplantation has been widely shown, their clinical efficiency in amyotrophic lateral sclerosis (ALS) is still to be proved. It is not only due to a limited number of studies, small treatment groups, and fast but nonlinear disease progression but also due to lack of objective methods able to show subtle clinical changes. Preliminary guidelines for cell therapy have recently been proposed by a group of ALS experts. They combine clinical, neurophysiological, and functional assessment together with monitoring of the cytokine level. Here, we describe a pilot study on transplantation of autologous adipose-derived regenerative cells (ADRC) into the spinal cord of the patients with ALS and monitoring of the results in accordance with the current recommendations. To show early and/or subtle changes within the muscles of interest, a wide range of clinical and functional tests were used and compared in order to choose the most sensitive and optimal set. Additionally, an analysis of transplanted ADRC was provided to develop standards ensuring the derivation and verification of adequate quality of transplanted cells and to correlate ADRC properties with clinical outcome.
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http://dx.doi.org/10.1155/2018/4392017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109475PMC
August 2018